温阳解郁汤对肾阳虚型抑郁大鼠PI3K/Akt信号通路及神经递质的影响
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篇名: 温阳解郁汤对肾阳虚型抑郁大鼠PI3K/Akt信号通路及神经递质的影响
TITLE: Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats
摘要: 目的 探讨温阳解郁汤对肾阳虚抑郁症大鼠磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路及神经递质的影响。方法将雄性SD大鼠分为空白组、模型组、氟西汀组(西药阳性对照,4.17mg/kg)、逍遥散组(中药阳性对照,1.88g/kg)和温阳解郁汤低、中、高剂量组(1.25、2.50、5.00g/kg),每组15只。除空白组外,其余各组均皮下注射皮质酮20mg/kg以复制肾阳虚型抑郁大鼠模型,并同时灌胃相应药液,每天1次,连续28d。观察大鼠的一般情况,检测其糖水偏好率、强迫游泳静止不动时间,计算其脏器指数,检测其血清中神经递质水平/含量,检测其海马组织中PI3K/Akt通路相关蛋白的表达量和树突棘数量。结果与空白组比较,模型组大鼠出现了掉毛、畏冷扎堆、蜷缩等症状,糖水偏好率,肾上腺、胸腺、脾指数,血清环磷酸腺苷(cAMP)、脑源性神经营养因子、γ氨基丁酸水平,cAMP与环磷酸鸟苷比值,去甲肾上腺素、多巴胺、5-羟色胺含量,PI3K、Akt、哺乳动物雷帕霉素靶蛋白的表达量,以及海马组织中树突棘数量均显著降低(P<0.01);静止不动时间、谷氨酸水平、糖原合成酶激酶3β蛋白的表达量均显著延长或升高(P<0.01)。与模型组比较,各药物组大鼠的抑郁症状有所改善,上述指标大部分逆转(P<0.05或P<0.01)。结论温阳解郁汤可改善大鼠的抑郁样行为和肾阳虚状态,调节神经递质的分泌,并可激活PI3K/Akt信号通路,从而起到保护海马神经元的作用。
ABSTRACT: OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group, model group, fluoxetine group (positive control of western medicine, 4.17 mg/kg), Xiaoyao powder group (positive control of TCM, 1.88 g/kg) and Wenyang jieyu decoction low-dose, medium-dose and high-dose groups (1.25, 2.50, 5.00 g/kg), with 15 rats in each group. Except for blank group, the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model, meanwhile the mice were given relevant medicine intragastrically, once a day, for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected, and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected, the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected, and the number of dendritic spines was determined. RESULTS Compared with blank group, model group suffered from the symptoms such as hair loss, fear of cold, curling up; sucrose preference rate, indexes of adrenal gland, thymus gland and spleen,serum levels of cyclic adenosine phosphate (cAMP), brain-derived neurotrophic factor and gamma-aminobutyric acid, the ratio of cAMP to cyclic guanosine monophosphate, the contents of norepinephrine, dopamine and 5-hydroxy-tryptamine, the expressions of PI3K, Akt, mammalian target of rapamycin, and the number of dendritic spines in the hippocampus were significantly decreased (P<0.01). The time of immobility, level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased (P<0.01). Compared with model group, depression symptoms of rats in each administration group were improved, and the above indexes were mostly reversed (P<0.05 or P<0.01). CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang, regulate the secretion of neurotransmitters, and activate PI3K/Akt signaling pathway, thus playing a role in protecting hippocampal neurons.
期刊: 2023年第34卷第06期
作者: 王旭艳;王鑫鑫;冯振宇;孟霜;马小娟;赵杰;赵建平
AUTHORS: WANG Xuyan,WANG Xinxin,FENG Zhenyu,MENG Shuang,MA Xiaojuan,ZHAO Jie,ZHAO Jianping
关键字: 温阳解郁汤;抑郁症;肾阳虚;磷脂酰肌醇3激酶/蛋白激酶B信号通路;神经递质;大鼠
KEYWORDS: Wenyang jieyu decoction; depression; kidney-yang deficiency; PI3K/Akt signaling pathway; neurotransmitter; rat
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